A. Field of the Invention
The present invention generally relates to methods and compositions useful for the debridement and treatment of wounds. More specifically, the present invention is related to enzymatic wound debridement compositions comprising Seaprose and methods of wound treatment using same.
B. Background of the Invention
The healing of wounds is a complex process which is often further complicated by the presence of nonviable necrotic tissue in the wound area. The presence of eschar and other necrotic tissue in a wound can impede the healing process causing the wound to become a slow-healing or “chronic” wound. Wounds such as diabetic foot ulcers, venous leg ulcers, arterial leg ulcers, decubitus ulcers, stasis ulcers, dermal ulcers, burns, and pressure ulcers are examples of wounds which can become chronic wounds with the presence of necrotic tissue that delays healing, and these wounds can be inhibited from healing.
Effective wound cleansing and debridement are long recognized prerequisites for optimal wound healing. Necrotic tissue present in a wound bed is undesirable because it may serve as a reservoir for bacterial growth, contain elevated levels of inflammatory mediators that promote chronic inflammation at the wound site, and impair cellular migration necessary for wound repair. It is increasingly well recognized that clearing a wound bed of necrotic tissue is an important step that may facilitate the healing process for a variety of wound types, particularly burn wounds and various chronic wounds.
A number of different modalities exist for wound debridement. The four most common debridement methods are surgical, autolytic, enzymatic, and mechanical. Each of these has its own benefits and shortcomings, depending on the wound type and the condition of the patient.
Enzymatic debridement is the process of topically applying an enzymatic debridement agent to the wound to digest eschar and other necrotic tissue, thereby facilitating removal of the necrotic tissue. Enzymatic debridement agents are those enzymes that can rapidly digest necrotic tissue without injury to living cells, thereby speeding the healing processes. Use of such debridement agents have included the employment of a wide variety of microbial, plant and animal materials, even things such as maggots or blowfly larvae, but more commonly, the enzyme papain derived from the papaya tree, the enzyme trypsin derived from animal pancreas, and the enzyme collagenase derived from the bacteria Clostridium histolyticum. The mechanism in almost all of these cases has been identified with enzymatic activity.
Healing of wounds is delayed by the presence of pus, tissue debris, bacteria, exudates and eschar. The major constituents of wound eschar are proteins, such as collagen, fibrin, elastin, fibronectin, and hemoglobin. Of these, various types of wound eschar have been demonstrated to be predominantly composed of the fibrous proteins collagen, elastin, and fibrin. The primary purpose of the debridement enzyme is to clean a wound of all of the various necrotic tissue elements and to thin out thick exudative secretions. When properly applied to selected patients, certain proteolytic enzymes cleanse infected proteinous surfaces of their inflammatory exudate without harm to living tissues, facilitate the drainage of areas of local purulent, sanguineous and fibrinous accumulations, promote the liberation of hidden bacteria, thereby exposing them to antimicrobial agents and native immune forces, and increase the rate of repair of previously infected wounds. This enzymatic action can also be of benefit for the treatment of inflammatory skin diseases such as psoriasis and eczema.
Topical ointment and cream compositions containing proteolytic enzymes such as papain, trypsin, and collagenase have been widely employed for enzymatic wound debridement particularly in patient populations not amenable to surgical debridement. Compositions containing thermolysin (US patent application 2003/0198631) and bromelain (U.S. Pat. No. 4,197,291) have also been disclosed for use in wound debridement.
An example of a commercially available enzymatic debridement ointment is one containing a bacterially derived collagenase used to degrade collagen components in wounds. Another product is one containing fibrinolysin which is specifically used to digest fibrin debris. These products contain enzymes that are potent and specific for their substrates. Such high debridement specificity results in less harm to viable tissue and less irritation to patients. However, since these enzymes are substrate specific, debridement of nonviable necrotic tissue may be slow or incomplete because of the various protein elements present in necrotic tissue of chronic wounds. For example, collagenase is very specific to digest collagens, but not very effective for other proteins. Likewise, fibrinolysin is specifically used to digest fibrin debris, but not very effective for other proteins.
Because of the diversity of proteins in wound eschar and other necrotic tissue, commercially available compositions containing nonspecific proteases, such as papain, were used for wound debridement with good clinical efficacy. However, most of these products are grandfathered (DESI) drugs and are no longer commercially available.